Release of methylene blue from graphene oxide-coated electrospun nanofibrous scaffolds to modulate functions of neural progenitor cells

Abstract

Transplantation of neural progenitor cells (NPCs) can repair the damaged neurons and therefore holds significant promise as a new treatment strategy for Alzheimer’s disease (AD). Development of functional scaffolds for the growth, proliferation, and differentiation of NPCs offers a useful approach for AD therapy. In our study, the functional scaffolds were obtained by fabrication of a poly(lactic-co-glycolic acid) (PLGA) nanofibrous mat by the electrospinning technique, followed by coating of a layer of graphene oxide (GO) and then physisorption of methylene blue (MB) under mild conditions. The precoating of GO on the nanofibrous scaffolds allows efficient loading and release of MB from the substrate for regulating the functions of NPCs. The NPCs cultured on the scaffolds remained in the quiescence phase due to the activation of autophagy signaling pathway by MB. Moreover, the MB-loaded nanofibrous scaffolds diminish tau phosphorylation and protect NPCs from apoptosis. Definitely, more work, especially the in vivo experiment, is highly desired to demonstrate the feasibility of the current strategy for AD treatment. Statement of SignificanceTransplantation of neural progenitor cells (NPCs) can repair the damaged neurons and hold significant promise as a new treatment strategy for Alzheimer’s disease (AD). Development of functional scaffolds for the growth, proliferation, and differentiation of NPCs offers a novel and useful approach for AD therapy. In this work, we have developed a GO and MB sequentially coated PLGA nanofibrous mat as a new scaffold for NPC transplantation and tauopathy inhibition. The coating of GO that we have demonstrated significantly enhanced the loading and release of MB on the scaffolds. Furthermore, NPCs cultured on the nanofibrous scaffolds entered quiescence phase through the activation of autophagy signaling pathway, leading to improved performance of NPCs to cope with stressors of disease. More importantly, the release of MB from the scaffolds leads to attenuation of tauopathy and protection of NPCs, which may represent a novel, versatile, and effective therapeutic approach for AD and other neurodegenerative diseases.